Propionate inhibition of succinate:CoA ligase (GDP) and the citric acid cycle in mitochondria.
Propionate inhibits oxygen consumption by rat liver mitochondria when glutamate, alpha-ketaglutarate, and succinate are substrates. Carnitine prevents this effect. The pattern of inhibition of 14CO2 release from metabolic intermediates indicates citric acid cycle inhibition between succinate:coenzyme A (CoA) ligase (GDP) and malate dehydrogenase. Propionyl CoA is synthesized from propionate in mitochondria. Propionyl CoA is a potent inhibitor of succinate:CoA ligase with positive cooperativity and half half-maximal inhibition at 2 X 10(-4) M propionyl CoA.
D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002331:Carnitine / Q000494:pharmacology; D002952:Citric Acid Cycle; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors*; D005971:Glutamates / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D010101:Oxygen Consumption; D011422:Propionates / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013389:Succinate-CoA Ligases / Q000037:antagonists & inhibitors*; D013386:Succinates / Q000378:metabolism
D000214:Acyl Coenzyme A; D005971:Glutamates; D008293:Malates; D011422:Propionates; D011773:Pyruvates; D013386:Succinates; D002245:Carbon Dioxide; C009061:propionyl-coenzyme A; D003066:Coenzyme A Ligases; D013389:Succinate-CoA Ligases; D002331:Carnitine